PAIP 2020: Microsatellite instability prediction in colorectal cancer.

Microsatellite instability (MSI) refers to alterations in the length of simple repetitive genomic sequences. MSI status serves as a prognostic and predictive factor in colorectal cancer. The MSI-high status is a good prognostic factor in stage II/III cancer, and predicts a lack of benefit to adjuvant fluorouracil chemotherapy in stage II cancer but a good response to immunotherapy in stage IV cancer. Therefore, determining MSI status in patients with colorectal cancer is important for identifying the appropriate treatment protocol. In the Pathology Artificial Intelligence Platform (PAIP) 2020 challenge, artificial intelligence researchers were invited to predict MSI status based on colorectal cancer slide images. Participants were required to perform two tasks. The primary task was to classify a given slide image as belonging to either the MSI-high or the microsatellite-stable group. The second task was tumor area segmentation to avoid ties with the main task. A total of 210 of the 495 participants enrolled in the challenge downloaded the images, and 23 teams submitted their final results. Seven teams from the top 10 participants agreed to disclose their algorithms, most of which were convolutional neural network-based deep learning models, such as EfficientNet and UNet. The top-ranked system achieved the highest F1 score (0.9231). This paper summarizes the various methods used in the PAIP 2020 challenge. This paper supports the effectiveness of digital pathology for identifying the relationship between colorectal cancer and the MSI characteristics.

Analysis of Platen Superheater Tube Degradation in Thermal Power Plants via Destructive/Non-Destructive Characteristic Evaluation.

Coal-fired power plants operating under Korea's standard supercritical pressure operate in a high-temperature environment, with steam temperatures reaching 540 °C. A standard coal-fired power plant has a 30-year design life, and lifespan diagnosis is performed on facilities that have operated for more than 100,000 h or 20 years. Visual inspection, thickness measurements, and hardness measurements in the field are used to assess the degree of material degradation at the time of diagnosis. In this study, aging degradation was assessed using an electromagnetic acoustic transducer to measure the change in transverse ultrasonic propagation speed, and the results were compared to microstructural analysis and tensile test results. Based on the experimental results, it was found that the boiler tube exposed to a high-temperature environment during long-term boiler operation was degraded and damaged, the ultrasonic wave velocity was reduced, and the microstructural grains were coarsened. It was also confirmed through tensile testing that the tensile and yield strengths increased with degradation. Our findings prove that the degree of change in mechanical properties as a function of the material's degradation state is proportional to the change in ultrasonic wave velocity.

The Pellino1-PKCθ Signaling Axis Is an Essential Target for Improving Antitumor CD8+ T-lymphocyte Function.

CD8+ T cells play an important role in the elimination of tumors. However, the underlying mechanisms involved in eliciting and maintaining effector responses in CD8+ T cells remain to be elucidated. Pellino1 (Peli1) is a receptor signal-responsive ubiquitin E3 ligase, which acts as a critical mediator for innate immunity. Here, we found that the risk of developing tumors was dependent on Peli1 expression. Peli1 was upregulated in CD8+ T cells among tumor-infiltrating lymphocytes (TIL). In contrast, a deficit of Peli1 enhanced the maintenance and effector function of CD8+ TILs. The development of Peli1-deficient CD8+ TILs prevented T-cell exhaustion and retained the hyperactivated states of T cells to eliminate tumors. We also found that Peli1 directly interacted with protein kinase C-theta (PKCθ), a central kinase in T-cell receptor downstream signal transduction, but whose role in tumor immunology remains unknown. Peli1 inhibited the PKCθ pathway by lysine 48-mediated ubiquitination degradation in CD8+ TILs. In summary, the Peli1-PKCθ signaling axis is a common inhibitory mechanism that prevents antitumor CD8+ T-cell function, and thus targeting Peli1 may be a useful therapeutic strategy for improving cytotoxic T-cell activity.

Model-based autonomous plate defects visualization method for quantitative wall-thinning estimation.

The visualization of the wall thinning of plate-like structures using scanning laser Doppler vibrometry (SLDV) is a promising method in nondestructive evaluation using laser ultrasonics. In particular, the Lamb-wave-based SLDV method that uses continuous excitation exhibits excellent performance for the estimation of the wall thinning of plates. Currently, plate thickness is quantitatively evaluated based on wavenumber analysis using measured signals. However, it is difficult to estimate plate thickness automatically below the product of frequency and thickness of 6 MHz·mm without knowing the wavenumber sensitivity and minimum wavenumber distance from reference mode owing to the lack of the physical understanding of Lamb waves. In this study, a model-based autonomous plate defects visualization method is proposed for the quantitative imaging of the wall thinning of plates so that inspectors can use scanning laser Doppler vibrometry (SLDV) without any knowledge of Lamb waves and its signal processing. Interdigital-transducer-based SLDV is utilized to validate the proposed method, and a 6-mm-thick carbon steel plate with 1-8% wall thinning, and a 2-mm-thick aluminum plate with Y-shaped wall thinning are used. Experiments demonstrate that the capability of the proposed method for detecting wall thinning in plates is equivalent to that of manual plate defects visualization method.

Ssu72 is a T-cell receptor-responsive modifier that is indispensable for regulatory T cells.

The homeostatic balance between effector T cells and regulatory T cells (Tregs) is crucial for adaptive immunity; however, epigenetic programs that inhibit phosphorylation to regulate Treg development, peripheral expression, and suppressive activity are elusive. Here, we found that the Ssu72 phosphatase is activated by various T-cell receptor signaling pathways, including the T-cell receptor and IL-2R pathways, and localizes at the cell membrane. Deletion of Ssu72 in T cells disrupts CD4+ T-cell differentiation into Tregs in the periphery via the production of high levels of the effector cytokines IL-2 and IFNγ, which induce CD4+ T-cell activation and differentiation into effector cell lineages. We also found a close correlation between downregulation of Ssu72 and severe defects in mucosal tolerance in patients. Interestingly, Ssu72 forms a complex with PLCγ1, which is an essential effector molecule for T-cell receptor signaling as well as Treg development and function. Ssu72 deficiency impairs PLCγ1 downstream signaling and results in failure of Foxp3 induction. Thus, our studies show that the Ssu72-mediated cytokine response coordinates the differentiation and function of Treg cells in the periphery.

Growth, puberty, and bone health in children and adolescents with inflammatory bowel disease.

BACKGROUND: Endocrine complications such as impaired growth, delayed puberty, and low bone mineral density (BMD) can be associated with inflammatory bowel disease (IBD) in children and adolescents. This study was performed to investigate the frequency, characteristics, and outcomes of endocrine complications of IBD in children and adolescents. METHODS: This study included 127 patients with IBD diagnosed before 18 years of age [117 with Crohn disease (CD) and 10 with ulcerative colitis (UC)]. Growth profiles, pubertal status, 25-hydroxyvitamin D3 [25(OH)D3] levels, and BMD were reviewed retrospectively. RESULTS: Short stature was observed in 14 of 127 (11.0 %) with a mean height-SDS of -2.31 ± 0.72. During a 2-year follow-up period, height-SDS did not significantly improve, while weight-SDS significantly improved. Among 109 patients who were older than 13 (girls) or 14 (boys) years of age during the study period, 11 patients (10.1 %) showed delayed puberty, which was associated with low weight-SDS. Vitamin D deficiency was documented in 81.7 % (94/115) with the average 25(OH)D3 level of 14.5 ± 7.0 ng/mL. Lumbar BMD Z-score was below - 2 SDS in 25 of 119 patients (21.0 %). Height-SDS, weight-SDS, and body mass index (BMI)-SDS were lower in patients with osteoporosis than those without osteoporosis. When pediatric CD activity index scores were high (≥ 30), weight-SDS, BMI-SDS, insulin-like growth factor 1 (IGF-1)-SDS, and testosterone levels were significantly decreased. CONCLUSIONS: Vitamin D deficiency and osteoporosis are common in pediatric IBD patients. As disease severity deteriorates, weight-SDS, IGF-1-SDS, and testosterone levels were decreased. Optimal pubertal development is necessary for bone health.

Living donor liver retransplantation for primary non-function of liver graft following multivisceral transplantation in a pediatric patient.

Multivisceral organ transplantation (MVOT) includes transplantation of three or more abdominal organs, generally including the small bowel, duodenum, stomach, liver, pancreas, and colon. We here presented the detailed procedures of repeat living donor liver transplantation for primary non-function of the first liver graft following MVOT in a pediatric patient. A 6-year-old girl with chronic intestinal pseudo-obstruction underwent MVOT with 5-year-old donor organs. However, the primary non-function of the liver graft developed, and an emergency living donor liver transplantation operation using a left lateral section graft was performed on the third day after MVOT. The donor was the patient's father. Portal flow interruption induced ischemic congestion of the whole small bowel, thus we used a series of porto- caval shunt to reduce the risk of ischemic splanchnic congestion during recipient hepatectomy and graft implantation. Other surgical procedures were the same as the standardized procedures for left liver graft implantation. The graft-recipient weight ratio was 2.15. The patient was managed conservatively for 3 months and discharged in an improved condition at 4 months after MVOT. She finally passed away at 22 months after MVOT. We think that our experience will be helpful for surgeons to cope with portal vein clamping-associated splanchnic congestion during liver transplantation and other abdominal surgeries.

Predominance of the c.648G > T G6PC gene mutation and late complications in Korean patients with glycogen storage disease type Ia.

BACKGROUND: Glycogen storage disease (GSD) Ia, caused by mutations in the glucose-6-phosphatase (G6PC) gene, is characterized by hepatomegaly, hypoglycemia, lactic acidosis, dyslipidemia, and hyperuricemia. This study aimed to investigate clinical and molecular features and late complications in Korean patients with GSD Ia. RESULTS: Fifty-four Korean patients (33 males and 21 females) from 47 unrelated families, who were diagnosed with GSD Ia, based on genetic and biochemical data, between 1999 and 2017, were included in this study. The median age at diagnosis was 3.9 years (range: 5 months to 42 years), and the follow-up period was 8.0 ± 6.8 years. Most patients presented with hepatomegaly during infancy, but hypoglycemic symptoms were not predominant. Genetic analysis showed that all the patients had at least one c.648G > T allele. Homozygous c.648G > T mutations in the G6PC gene were identified in 34 families (72.3%), and compound heterozygotes with c.648G > T were found in the other families. The allele frequency of c.648G > T was 86.2% (81/94), and p.F51S, p.R83H, p.G122D, p.Y128*, p.G222R, and p.T255A were identified. Of 26 adult patients, 14 had multiple hepatic adenomas, and two were diagnosed with hepatocellular carcinoma. Thirteen patients showed renal complications, and seven patients presented gout, despite preventive allopurinol treatment. Twelve patients had osteoporosis, and two patients had pulmonary hypertension. The final heights were 157.9 cm (standard deviation score: - 3.1) in males and 157.8 cm (standard deviation score: - 0.6) in females. CONCLUSION: In our Korean patients with GSD Ia, the most common mutation in the G6PC gene was c.648G > T, suggesting a founder effect. Because of only mild hypoglycemia, the patients tended to be diagnosed late. Thus, adult patients with GSD Ia eventually developed diverse and serious complications, which indicates a need for careful monitoring and proper management of this disease.

Wedged-patch venoplasty of the left liver graft portal vein for size matching in pediatric living donor liver transplantation.

Portal vein (PV) size matching between recipient and liver graft is important in preventing anastomotic stenosis in living donor liver transplantation (LDLT). In right liver grafts, the diameter of graft PV is usually >10 mm. Thus, PV size matching does not become critical in adult recipients. If the recipient PV is very large, funneling fence can be attached to graft PV. However, if the diameter of graft PV is <8 mm, it can induce anastomotic stenosis. We experienced a few cases of PV anastomotic stenosis due to small-sized graft PV in >5000 LDLT cases, but graft PV widening was not performed because graft PV is considered as being a no-touch area. In thinking out of the box, we performed wedged-patch venoplasty to exceptionally narrow graft PV. A 4 year-old female patient underwent second LDLT due to progressive deterioration of graft function after 3 years. At first LDLT operation for biliary stresia, an iliac vein conduit was interposed for PV reconstruction. At second LDLT operation, the diameter of interposed PV was 10 mm, but the left liver graft PV was only 6 mm-sized. Uniquely, the left PV was waist only at first-order PV. To resolve this PV waist, a longitudinal incision was made to release the waist. A cold-preserved fresh iliac vein patch was inserted to widen the PV orifice. The patch size was adjusted to match the size of the recipient PV. The patient recovered uneventfully. This wedged-patch venoplasty technique can be applied to small-sized graft PV, to cope with PV size mismatching in LDLT.

On-Line Monitoring of Pipe Wall Thinning by a High Temperature Ultrasonic Waveguide System at the Flow Accelerated Corrosion Proof Facility.

Pipe wall thinning and leakage due to flow accelerated corrosion (FAC) are important safety concerns for nuclear power plants. A shear horizontal ultrasonic pitch/catch technique was developed for the accurate monitoring of the pipe wall-thickness. A solid couplant should be used to ensure high quality ultrasonic signals for a long operation time at an elevated temperature. We developed a high temperature ultrasonic thickness monitoring method using a pair of shear horizontal transducers and waveguide strips. A computer program for on-line monitoring of the pipe thickness at high temperature was also developed. Both a conventional buffer rod pulse-echo type and a developed shear horizontal ultrasonic waveguide type for a high temperature thickness monitoring system were successfully installed to test a section of the FAC proof test facility. The overall measurement error was estimated as ±15 µm during a cycle ranging from room temperature to 150 °C. The developed waveguide system was stable for about 3300 h and sensitive to changes in the internal flow velocity. This system can be used for high temperature thickness monitoring in all industries as well as nuclear power plants.

Magnetostrictive Guided Wave Technique Verification for Detection and Monitoring Defects in the Pipe Weld.

During inspection of piping in nuclear power plants or other industries, it is difficult to implement conventional nondestructive techniques due to limited accessibility or obstacles such as pipes with insulation, pipes buried underground, structural complexity, or radiation environments. In addition, since the defects mainly occur in the weld region or support area, it is not easy to separate defect signals from those of structural components. To solve these problems, we developed a technique to detect and monitor the formation and growth of defects, using a magnetostrictive guided wave sensor. This sensor has advantages (such as sharp and clear signal patterns and ability to easily eliminate the signal from the geometric structure) over the conventional piezoelectric transducer. To verify our technique, signals from actual pipe welds with defects were acquired and processed with our phase matching/subtraction program. The proposed technique shows a superior capability for detection and monitoring of defects, compared to the conventional guided wave methods.

Conditional random fields for clinical named entity recognition: A comparative study using Korean clinical texts.

BACKGROUND: This study demonstrates clinical named entity recognition (NER) methods on the clinical texts of rheumatism patients in South Korea. Despite the recent increase in the adoption rate of the electronic health record (EHR) system in global health institutions, health information technologies for handling and acquisition of information from numerous unstructured texts in the EHR system are still in their developing stages. The aim of this study is to verify the conventional named entity recognition (NER) methods, namely dictionary-lookup-based string matching and conditional random fields (CRFs). METHODS: We selected discharge summaries for 200 rheumatic patients from the EHR system of the Seoul National University Hospital and attempted to identify heterogeneous semantic types present in the clinical notes of each patient's history. RESULTS: CRFs outperform string matching in extracting most semantic types (median F1 = 0.761, minimum = 0.705, maximum = 0.906). String matching is found to be better suited for identifying hospital visit information. The performance of both methods is comparable for identifying medications. The 10-fold cross-validation shows that CRFs had median F1 = 0.811 (minimum = 0.752, maximum = 0.918), and exhibited good performance even when trained with simple features. CONCLUSION: CRFs are a good candidate for implementing clinical NER in Korean clinical narrative documents. Increasing the training data and incorporating sophisticated feature engineering might improve the accuracy of identifying health information, enabling automated patient history summarization in the future.

Developing Methodologies to Find Abbreviated Laboratory Test Names in Narrative Clinical Documents by Generating High Quality Q-Grams.

Laboratory test names are used as basic information to diagnose diseases. However, this kind of medical information is usually written in a natural language. To find this information, lexicon based methods have been good solutions but they cannot find terms that do not have abbreviated expressions, such as "neuts" that means "neutrophils". To address this issue, similar word matching can be used; however, it can be disadvantageous because of significant false positives. Moreover, processing time is longer as the size of terms is bigger. Therefore, we suggest a novel q-gram based algorithm, named modified triangular area filtering, to find abbreviated laboratory test terms in clinical documents, minimizing the possibility to impair the lexicons' precision. In addition, we found the terms using the methodology with reasonable processing time. The results show that this method can achieve 92.54 precision, 87.72 recall, 90.06 f1-score in test sets when edit distance threshold(τ) = 3.

Variant meso-Rex bypass with transposition of abdominal autogenous vein for the management of idiopathic extrahepatic portal vein obstruction: a retrospective observational study.

BACKGROUND: The aim of this study was to evaluate whether variant meso-Rex bypass with transposition of abdominal autogenous vein can be used as an alternative treatment modality for selected patients with symptomatic extrahepatic portal vein obstruction. METHODS: This was a retrospective review of six consecutive patients who received this alternative procedure for the treatment of symptomatic portal hypertension secondary to idiopathic extrahepatic portal vein obstruction. Their clinical characteristics, operative procedures and outcomes were analyzed retrospectively. RESULTS: The procedure was attempted in six patients, and all had a patent shunt established by intraoperative portography at the end of the procedure; the coronary vein was used in four patients and the inferior mesenteric vein was used in two. During the median period of 23.5 months (range 10-30 months), follow-up was uneventful except one patient; reduced portal hypertension and no new episodes of gastrointestinal bleeding were observed in all patients, with the exception of one patient with shunt stenosis and recurrent varix bleeding who had to undergo endovascular treatment to restore portal vein blood flow. Technical and clinical success was achieved in all patients. CONCLUSIONS: This procedure could be used safely and effectively to treat selected patients with portal hypertension secondary to extrahepatic portal vein obstruction.

Use of meso-Rex shunt with transposition of the coronary vein for the management of extrahepatic portal vein obstruction.

The meso-Rex shunt is used to safely and effectively treat patients with portal hypertension due to extrahepatic portal vein obstruction. In the standard meso-Rex shunt technique, the patient's own internal jugular vein is used as a vascular autograft. Inevitably, such a procedure requires neck exploration and sacrifice of the internal jugular vein. Here, we present a case of a 20-year-old man with idiopathic extrahepatic portal vein obstruction, who was treated with a new technique of transposition of the coronary vein, which is enlarged in most cases of portal hypertension, as an alternative to the standard meso-Rex shunt technique. The transposition of the coronary vein into the Rex recessus is more efficient and less invasive than harvesting an autologous vein graft. Therefore, this technique simplifies the procedure and should be used when possible.

Management of late-onset portal vein complications in pediatric living-donor liver transplantation.

The purpose of this study was to evaluate retrospectively the results of PTA for late-onset PV complications after pediatric LDLT and to assess whether a meso-Rex shunt is a viable option for treating restenosis of the PV after PTA in selected cases. Seventy-five children who underwent adult-to-child LDLT were included in this study, and there were six late-onset PV complications (8.0%). The initial therapeutic approach was PTA, with or without stent: PTA with balloon dilation for three children, PTA with stent placement for one child, and failure to cannulate the occluded PV for two children. A meso-Rex shunt was performed in the two children after failed PTA: One suffered complete obstruction of the main PV, and the other, restenosis with total thrombosis after PTA with stent. The PTA was a technical and clinical success in four with PV stenosis of the six patients (66.7%), and successful application of a meso-Rex shunt in the other two children resulted in restoration of PV flow. In conclusion, PTA is a safe and effective procedure for treating late-onset PV stenosis after pediatric LDLT. However, in growing pediatric recipients with restenosis of the PV after PTA or chronic PV thrombosis, a meso-Rex shunt may be a better choice for late-onset PV complications.

Identification of novel ATP7B gene mutations and their functional roles in Korean patients with Wilson disease.

Wilson disease (WND), an autosomal recessive disorder of copper transport, is characterized by excessive accumulation of intracellular copper in liver and extrahepatic tissues because of impaired biliary copper excretion and disturbed incorporation of copper into ceruloplasmin. Hepatic cirrhosis and neuronal degeneration are the major symptoms of WND, and mutations in the ATP7B gene are associated with WND. We have identified 28 different mutations in the ATP7B gene, including six novel variations, in 120 unrelated Korean patients with WND. Molecular defects in ATP7B were present in only 75.0% of Korean WND patients, with the most common mutation, p.Arg778Leu, having an allele frequency of 39.2%. To evaluate the functional defects of ATP7B caused by novel mutations, we used a yeast complementation system, and we used confocal microscopy to localize each mutation after transient expression in mammalian cells. Six novel variations were cloned into a yeast expression vector and two into a mammalian expression vector for confocal analysis. We found that c.2785A>G (p.Ile929Val) and c.3316G>A (p.Val1106Ile) were rare polymorphisms, whereas the others were novel variations disturbing ATP7B function.

Lessons learned from 1,000 living donor liver transplantations in a single center: how to make living donations safe.

Serious complications have occurred in a considerable proportion of living donors of liver transplants, but data from a single high-volume center has rarely been available. We analyzed the medical records of donors and recipients of the first 1,000 living donor liver transplants, performed at Asan Medical Center from December 1994 to June 2005, with a focus on donor safety. There were 107 pediatric and 893 adult transplants. The most common diagnoses were biliary atresia in pediatric recipients (63%) and hepatitis B-associated liver cirrhosis (80%) in adult recipients. Right lobe donors were strictly selected based on liver resection rate and steatosis. From 1,162 living donors, 588 right lobes, 6 extended right lobes, 7 right posterior segments, 464 left lobes, and 107 left lateral segments were obtained. Of these, 837 grafts were implanted singly, whereas 325, along with 1 cadaveric split graft, were implanted as dual grafts into 163 recipients. The 5-yr survival rates were 84.8% in pediatric recipients and 83.2% in adult recipients. There was no donor mortality, but 3.2% of donors experienced major complications. Until the end of 2001, the major donor complication rate was 6.7%, with most occurring in right liver donors. Since 2002, liver resection exceeding 65% of whole liver volume were avoided except for young donors with no hepatic steatosis, and the donor complication rate has been reduced to 1.3%. In conclusion, a majority of major living donor complications appear to be avoidable through the strict selection of living donor and graft type, intensive postoperative surveillance, and timely feedback of surgical techniques. Selection of right lobe graft should be very prudently considered if the donor right liver appears to be larger than 65% of the whole liver volume.